chr20-32210196-AG-A

Position:

• chr20-32210196-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_015352.2(POFUT1):​c.246+5del variant causes a splice donor 5th base, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POFUT1 NM_015352.2 splice_donor_5th_base, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.28

Genes affected

POFUT1 (HGNC:14988): (protein O-fucosyltransferase 1) This gene encodes a member of the glycosyltransferase O-Fuc family. This enzyme adds O-fucose through an O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-fucose glycans are involved in ligand-induced receptor signaling. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 20-32210196-AG-A is Pathogenic according to our data. Variant chr20-32210196-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 3252104.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POFUT1	NM_015352.2	c.246+5del		splice_donor_5th_base_variant, intron_variant		ENST00000375749.8	NP_056167.1
POFUT1	NM_172236.2	c.246+5del		splice_donor_5th_base_variant, intron_variant			NP_758436.1
POFUT1	XM_047440079.1	c.-79+2132del		intron_variant			XP_047296035.1
POFUT1	XR_007067447.1	n.308+5del		splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8	c.246+5del		splice_donor_5th_base_variant, intron_variant		1	NM_015352.2	ENSP00000364902	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dowling-Degos disease 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

ClinVar Staff, National Center for Biotechnology Information (NCBI)

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.97		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-30797999;